Protein tyrosine phosphatases (PTPs) play vital roles in numerous cellular processes and are implicated in a growing number of human diseases, ranging from cancer to cardiovascular, immunological, infectious, neurological, and metabolic diseases. The Vaccinia H1-related (VHR) PTP is a dual-specific Erk and Jnk phosphatase, the loss of which causes specific cell cycle arrest in HeLa carcinoma cells, suggesting that VHR inhibition may be a useful approach to halt the growth of cancer cells without detrimental effects on normal cells. Recent studies by collaborators and us suggest that VHR is upregulated in several cervix cancer cell lines, in squamous intraepithelial lesions, and squamous cell carcinomas of the uterine cervix. High throughput chemical library screening will be used to identify hit compounds, which will be then further developed into potent and specific inhibitors of VHR. These inhibitors will be useful chemical probes for basic research into the mechanisms of signal transduction and mitogen-activated protein (MAP) kinase regulation, and may also establish VHR as a novel and promising drug target for the treatment of cervical cancer. Besides a screening ready HTS assay, we also have a secondary assay, profiling assays, and cell-based assays in place to verify, characterize, and prioritize hits. We have milligram amounts of highly pure VHR in hand, so that HTS for VHR inhibitors could commence immediately. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to seek access to high-throughput chemical library screening to identify hit compounds for the protein tyrosine phosphatase (PTP) VHR, which we will then further develop into potent and specific inhibitors of VHR. PTPs have been recently implicated with numerous human diseases, including cancer. Recent studies by our lab and others clearly suggest that VHR is critical for the development of cervical cancer. [unreadable] [unreadable] [unreadable]